Whereas the role of leukocyte-chemotaxis in inflammation and infections has been studied extensively, there appears to be no recorded literature of studies concerned with the in vivo role of bacterial chemotaxis. Our current data, detailed in this application, indicate that bacterial chemotaxis had a significant effect on virulence and/or intestinal growth of cholera vibrios in all three of the in vivo systems tested to date. We propose now to study the mechanisms by which chemotaxis exerts its in vivo effect. Initially three possible mechanisms will be investigated: (a) Chemotactic bacteria may be attracted to the mucosal surface by chemotactively attractive substances (taxins) emanating from the mucosa. (b) Chemotactic bacteria may be attracted to food particles undergoing digestion, thereby gaining an advantage in the competition for nutrients which occurs in the large intestine and (c) Chemotactic bacteria may avoid areas containing high concentrations of inhibitors such as short-chain fatty acids in the intestinal microenvironment. Several lines of evidence, detailed in this application, suggest that the natural presence of toxins in certain diets, or the addition of toxins to diets, may reverse the advantage which chemotactic bacteria normally enjoy in the intestine and thereby offer a measure of protection to the host. The chemical nature of the toxins involved will therefore be studied. The possible role of chemotaxis in the interaction of other bacteria (e.g., Salmonella, enteropathogenic E. coli, Proteus or Pseudomonas) with the experimental host will be studied in enteric infections as well as infections of burn wounds, urinary tract infections and systemic infections. Finally, the role of chemotaxis in the ecology of motile bacteria of the indigenous intestinal flora will be investigated.